title: Anterior definitive endoderm from ESCs reveals a role for FGF signaling.
abstract: The use of embryonic stem cell (ESC) differentiation to generate functional hepatic or pancreatic progenitors and as a tool for developmental biology is limited by an inability to isolate in vitro equivalents of regionally specified anterior definitive endoderm (ADE). To address this, we devised a strategy using a fluorescent reporter gene under the transcriptional control of the anterior endoderm marker Hex alongside the definitive mesendoderm marker Cxcr4. Isolation of Hex(+)Cxcr4(+) differentiating ESCs yielded a population expressing ADE markers that both can be expanded and is competent to undergo differentiation toward liver and pancreatic fates. Hex reporter ESCs were also used to define conditions for ADE specification in serum-free adherent culture and revealed an unexpected role for FGF signaling in the generation of ADE. Our findings in defined monolayer differentiation suggest FGF signaling is an important regulator of early anterior mesendoderm differentiation rather than merely a mediator of morphogenetic movement.
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JQ, UK. gmm38@cscr.cam.ac.uk
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Morrison
authors.forename: Ifigenia
authors.initials: I
authors.lastname: Oikonomopoulou
authors.forename: Rosa Portero
authors.initials: RP
authors.lastname: Migueles
authors.forename: Shamit
authors.initials: S
authors.lastname: Soneji
authors.forename: Alessandra
authors.initials: A
authors.lastname: Livigni
authors.forename: Tariq
authors.initials: T
authors.lastname: Enver
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Brickman
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D004707:Endoderm / Q000166:cytology / Q000502:physiology*; D051519:Fibroblast Growth Factor 4 / Q000378:metabolism*; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010179:Pancreas / Q000166:cytology / Q000502:physiology; D011401:Promoter Regions, Genetic; D019718:Receptors, CXCR4 / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D000943:Antigens, Differentiation; C514936:CXCR4 protein, mouse; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D019718:Receptors, CXCR4; D014157:Transcription Factors